Transforming growth factor-β1-regulated Fas/FasL pathway activation suppresses nucleus pulposus cell apoptosis in an inflammatory environment.

Abstract

BACKGROUND:

During disc degeneration, inflammatory cytokine tumor necrosis factor (TNF)-α is correlated with nucleus pulposus (NP) cell apoptosis. Transforming growth factor (TGF)-β1 has the potential to regenerate degenerative disc.

OBJECTIVE:

To investigate the protective role of TGF-β1 against TNF-α-mediated NP cell apoptosis and the underlying mechanism.

METHODS:

Rat NP cells were treated with TNF-α (100 ng/ml) for 48 h. TGF-β1 was added into the culture medium to investigate its protective effects against TNF-α-induced NP cell apoptosis. Exogenous FasL was used to investigate the potential role of the Fas/FasL pathway in this process. Flow cytometry assay was used to analyze NP cell apoptosis. Real-time PCR and Western blotting were used to analyze gene and protein expression of apoptosis-related molecules.

RESULTS:

In TNF-α-treated NP cells, TGF-β1 significantly decreased NP cell apoptosis, declined caspase-3 and -8 activity, and decreased expression of Bax and caspase-3 (cleaved-caspase-3) but increased expression of Bcl-2. However, exogenous FasL partly reversed these effects of TGF-β1 in NP cells treated with TNF-α. Additionally, expression of Fas and FasL in TNF-α-treated NP cells partly decreased by TGF-β1, whereas exogenous FasL increased expression of Fas and FasL in NP cells treated with TGF-β1 and TNF-α.

CONCLUSION:

TGF-β1 helps to inhibit TNF-α-induced NP cell apoptosis and the Fas/FasL pathway may be involved in this process. The present study suggests that TGF-β1 may be effective to retard inflammation-mediated disc degeneration.

• Authors: Jingjing Xie, Bo Li, Bing Yao, Pingchao Zhang, Lixin Wang, Hua Lu, Xuan Song
• Journal: Bioscience reports (Biosci Rep) Vol. 40 Issue 2 (02 28 2020) ISSN: 1573-4935 [Electronic] England
• PMID: 31808511 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Apoptosis Regulatory Proteins
• Fas Ligand Protein
• Fas protein, rat
• Faslg protein, rat
• Transforming Growth Factor beta1
• Tumor Necrosis Factor-alpha
• fas Receptor

Topics

• Animals
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Cells, Cultured
• Fas Ligand Protein (metabolism, pharmacology)
• Female
• Intervertebral Disc Degeneration (drug therapy, genetics, metabolism, pathology)
• Male
• Nucleus Pulposus (drug effects, metabolism, pathology)
• Rats, Sprague-Dawley
• Signal Transduction
• Transforming Growth Factor beta1 (pharmacology)
• Tumor Necrosis Factor-alpha (pharmacology)
• fas Receptor (metabolism)